Ischemic injury of the myocardium occurs in a variety of pathophysiologic states as well as in the operating room during cardiac surgery. The objective of this research is to investigate the ability of some pharmacological agents to offer protection to the ischemic myocardium. To perform this objective the myocardium will be made ischemic by two basic methods: 1) hypotension which reduces coronary perfusion pressure and blood flow, 2) acute infarction by ligation of a portion of the left anterior descending branch of the left coronary artery. The dog will be used as the animal model. Regional distribution of blood flow in the myocardium will be measured using 7-9 micron radioactive microspheres. Transcapillary exchange of lipid-insoluble substances will be made using the indicator diffusion technique. Pharmacologic agents (a new series of dopamine analogues, and nitrites) will be administered either by intravenous injection in a bolus or continuous intravenous infusion. Measurements of regional myocardial blood flow and transcapillary exchange will be made in the control state, after an ischemic stress and after administration of a given agent. It is envisioned that this project will study both short (1-3 hours) and long term (1-3 days, 3-6 weeks) effects of the pharmacologic agents. The long term studies are particularly adaptable to those experiments with myocardial infarction. Histologic measurements of the myocardium will be made to correlate with physiologic data. Electron microscopy will be used to define the sequence and magnitude of changes in cellular organelles and inclusions concerned with cell function. Histochemistry will be used to characterize focal and regional alterations indicative of pre-necrotic, necrotic and hypoxic states. The capillary bed will be studied with reference to quantitative morphology, permeability and vesicular transport. These studies are designed to study functional and structural clanges in the ischemic myocardium before and after administration of pharmacologic agents to determine if, and how, such agents provide protection for the ischemic myocardium.